Therapeutic intravenous fat compositions



United States Patent THERAPEUTIC INTRAVENOUS FAT COMPOSITIONS NoDrawing. Original application Apr. 30, 1956, Ser. No. 581,269. Dividedand this application Sept. 5, 1957, Ser. No. 682,081

7 Claims. (Cl. 167-66) tions, amounting to approximately thirty percentof the patients treated. These reactions consist of chills, fever,backache, chest pain, nausea, vomiting, dyspnea, apnea, blood pressureeffects and the like. The reactions are all the more troublesome becausemany of them are not observed in the usual laboratory animals. It hasnow been discovered that a particular soya phosphatide fraction willproduce suitable intravenous fat emulsion which significantly reducesthe number of the previously indicated undesirable reactions.

It is therefore an object of the present invention to provide atherapeutic fat product which is especially well-suited for intravenoususe in human beings or animals. Another object of the present inventionis to provide a therapeutic fat product which is physically andchemically stable and which has significantly fewer undesirablereactions than previously existing products when administeredintravenously to human beings. A further object is the provision ofsuch'a product which has a much lower incidence of clinical reactions,such as chills, backache, chest pain, nausea, vomiting, dyspnea, apnea,blood pressure effects, and the like, when used intravenously in humanbeings. Still another object is the provision of a new, essentiallyunreaetive soya phosphatide fraction which can b e.used as an emulsifierfor an intravenous fat product. A further object is the provision of aprocess for the preparation of such a soya phosphatide fraction. Otherobjects will be apparent to one skilled in the art to which thisinvention pertains.

The foregoing and additional objects have been accomplished by theprovision of a therapeutic fat product which is especially suitable forintravenous use in human beings and which comprises a metabolizable,nontoxic, fixed oil emulsified in an aqueous vehicle by astable soyaphosphatide fraction (1) which does not depress blood pressure wheninjected into anesthetized cats, and (2) which can be prepared byabsorbing the undesirable reactive materials found in themonatomic,lower molecular weight aliphatic alcohol-soluble soya phosphatides on anadsorbent selected from the group consisting of aluminum oxide,magnesium oxide and activated carbon. It is preferred that aco-emulsifier be used with the soya phosphatide fraction of the presentcomposition. The ethylene oxide-polypropylene glycol condensationproduct more particularly described in co-pending application t We t o 9.3 1 sxes a ut ,fifl perssm ut Patented Mar. 28, 1961 ,Serial No.456,637, now U.S. Patent No. 2,870,019, is most suitable for thepurpose, although other co-emulsifiers maybe used satisfactorily. Thecondensation productis characterized as a polyalkyleneglycol in whichthe alkylene units consist of ethylene and propylene found 'to bemostfsuitable are cottonseed oil, olive oil,

peanut oil, coconut oil, sesame oil, corn oil and the like. An exampleof a suitable synthetic oilis that disclosed in U.S. Patent No.2,728,706. going oils can also be used. Cottonseed oil and olive:oila're preferred.

' The physical stability of the emulsion of these oils is important.Particles of these oils should be less than about 2.5 microns indiameter and preponderantly below about 0.5 micron in diameter. Theseparticle sizes should be stable under various test conditions consideredvalid indicators of physical stability for pharmaceutical fat emulsions.

isotonic agents are desirable for introvenous fat productssincethey-im-part proper tonieity to the emulsion. Metabolizable sugarsand polyhydroxyalcohols are wellsuited for this purpose. Suitable sugarsare the monosaccharides, such as glucose (dextrose) and fructose.

Suitable polyhydroxy alcohols include sorbi-tol.

' The ethylene oxide-polypropylene glycol condensation product used asco-emulsifier in the fat product is defined in U.S. Patent No. 2,674,619and co-pending application Serial No. 456,637, filed September" 16,1954.

They are represented by the following formula:

2H4 )a( 3 6 )b( 2 e )c wherein a, b and c are positive integers whichcanbe varied over a wide range. Within the limitations inherent in thepreferred composition of the present invention, it is desirable to use aformula having a base molecular' weight between about 1500 and aboutlSOO with between about eighty and about ninety percent ethylene oxidein the molecule. The base is the polypropylene glycol unit. Such aformula can also be designated Wyandotte Chemical Corporation.

An antioxidant can be added to prevent oxidation of;

thebils during processing and Tancidity during storage. Metabolizableantioxidants of the phenolic type, such as tertiary butyl anisoles andthe like, are suitable. It

is preferred to use a combination of tertiary bu-tyl-4'-hydroxyanisole,propylgallate, and citric acid.

The concentrations of various ingredients which can be utilized in thepresent composition can be carried over a wide range. However, thedesirable overall characteristics tend to limit somewhat the permissiblevariations of the concentration of the particular ingredients. One suchcharacteristic is the caloric value of the fat and sugar in anyparticular combination. Another character- W w sh't nd .t i tli amoun -ph; ins qd ntsj s the viscosity of the suspension. It isnot desirable.hat

Mixtures of the fore-' otherwise the product tends to be too viscous forinjection. From the caloric standpoint, the lower limit for anintravenous product such as the present composition is about ten percentwt./vol. The preferred concentration of oil is about fifteen to about 25percent wt./vol. for intravenous use. The concentration of sugar in thecomposition of the present invention should be between about threepercent and ten percent wt./vol. of the water, preferablyrabout fivepercent.

Although the therapeutic fat product of the present invention isprimarily designed for intravenous use, the composition can also be usedorally. However, a successful oral product would not require that thephosphatides be processed to the same extent as for an intravenousproduct. The concentrations indicated above would, of course, besomewhat different for an oral product than for an intravenous product.

Once the concentrations of the oils and sugars have been fixed withinthe ranges specified above, the concentration of the soya phosphatidefraction for intravenous use can be varied between about 0.5 to aboutthree percent wt./vol. (1.2 percent preferred). The concentration of thepreferred ethylene oxide-polypropylene glycol condensation product canbe varied from about 0.2 to about 0.5 percent wt./vol. (0.3 percentpreferred) for the intravenous product. Thus, the amounts of theemulsifiers utilized in the composition of the present invention dependsupon the amount of oil chosen.

In carrying out the process of preparing the soya phosphatide fractionof the present invention, commercially available soya phosphatides, suchas Lecithin RG (Glidden), or the alcohol-soluble fraction of soyaphosphatides (e.g., Lecithin RAS, Glidden) can be used as startingmaterial. It is desirable that each of these products be extracted witha monatomic, lower molecular weight aliphatic alcohol, e.g., methanol,ethanol, propanol, isopropanol, or mixtures thereof. Ethanol ispreferred, partly because of higher yield and partly because it is lesstoxic if incompletely removed from the product. It is preferred thatthis extraction be carried out at about room temperature. Absoluteethanol need not be used. In fact alcohol U.S.P. (not less than 94.9percent by volume of C H OH) is preferred. If thirty percent or morewater is used, however, the desirable phosphatide fraction will alsopartially precipitate out. Thus, ethanol in a concentration of 85 to 100percent is operative.

This alcohol-soluble fraction is not entirely satisfactory since itstill contains reactive substances which, when made up into a fatemulsion for intravenous use, causes the undesirable clinical reactionsnoted above. It is necessary, therefore, that the alcohol-solublefraction be contacted with an adsorbent selected from the groupconsisting of aluminum oxide, magnesium oxide and activated carbon.Acid-washed carbon should be avoided. The harmful substances remainadsorbed on the adsorbent, and the soya phosphatide fraction whichremains dissolved in the alcohol will not only provide a suitableemulsifier for the intravenous fat product of the present invention, butwill also eliminate or significantly reduce such undesirable effects aschills, backache, chest pain, nausea, vomiting, dyspnea, apnea, bloodpressure effects and the like, when made up into a fat emulsion.

In the preferred embodiment of the process of purification, theethanol-soluble portion of soya phosphatide in about ten vol./wt. ofethanol is stirred with about two parts by weight of aluminum oxide forabout thirty minutes at room temperature. The adsorption time can bereduced to as little as ten minutes, and the adsorption will still besatisfactory. When the aluminum oxide is reduced in quantity to as lowas 1.5 parts by weight, the product produced is unsatisfactory. Afterthe aluminum oxide is filtered out, the alcohol is removed under reducedpressure, and the material is taken up in an appropriate amount ofvegetable oil for the preparation of an emul- 81011.

Med. 34, 688 (1949).

A suitable screen to determine the clinical reactiveness of the soyaphosphatide fraction is the test for blood depressor effects in cats. Ifthe blood depressor effect is not observed in an anesthetized cat, thematerial tested will not possess such undesirable reactions whenadministered to humans. The cat test referred to herein is substantiallythat described by Geyer et al., J. Lab. Clin. Geyer et al. reported thatthe phosphatide fraction prepared by the use of solvents was nonreactivein cats when freshly prepared. However, emulsions prepared with thismaterial became reactive within four days. The soya phosphatide fractionuseful in the composition of the present invention does not becomereactive when used in an emulsion even though stored for a considerableperiod of time.

In carrying out the cat test a cat is anesthetized with sodium salt of 5ethyl-5-(l-methylbutyl)-barbituric acid. The jugular vein and carotidartery are canulated. The carotid artery is connected to a merclurymanometer equipped to record blood pressure. An intravenous injection ofthe material to be tested, e.g., a soya phosphatide fraction, is addedvia the juglar canula, and the blood pressure is recorded, noting therise or fall. If a fall in pressure is to occur at all, it will occuralmost immediately after injection.

The chemical composition of the soya phosphatide fraction of the presentinvention cannot be characterized exactly. This is generally true of anymixture of phosphatides derived from natural sources. The complexity ofthe problem is shown by many papers appearing in the literature, e.g.,Scholfield et al., J. Am. Oil. Chem. Soc., 25, 368 (1948). However, fromthe standpoint of reproductibility and practical utilization, the soyaphosphatide fraction can be characterized as a stable fraction of soyaphosphatides (1) which does not depress blood pressure when injectedinto anesthetized cats, (2) which can be prepared by adsorbing theundesirable reactive materials found in the monatomic, lower molecularweight aliphatic alcohol-soluble soya phosphatides on an adsorbentselected from the group consisting of aluminum oxide, magnesium oxideand activated carbon, and (3) which is a satisfactory emulsifier for theoil used in a therapeutic fat product.

In addition, the sola phosphatide fraction can be characterizedchemically sufficiently to differentiate it from the whole soyaphosphatides and other fractions thereof. The general structure ofphosphatides is represented by the following structural formula:

wherein the Rs represent fatty acids which have been found by Hilditchand Pedelty (Wittcofi, The Phosphatides, Reinhold Publishing Corp.,1951, p. 223) to be present in soybean phosphatides as:

Percent Palrnitic 1 1.7

Stearic 4.0

Arachidic 1.4

Hexadecennic 8.6

Oleic 5.5

T innleir' 63,3

C unsat 5 .5

1 Includes some llnolenic.

In lecithin R=cho1ine.

yww.

.zwas shaken thirty minutes.

aa' aa s In cephalins R=,ethanolamine, serine or inositol, although inthe case ofinositol this structure is an oversimplification.

Total nitrogen is therefore a measure of all the phosphatides (if thatis all the nitrogen-containing material that is present) exceptphosphatidylinositol.

Total phosphorus is likewise such a measure, and further, for eitherpure lecithin, phosphatidylserine or phosphatidylethanolamine, themolecular ratio of N to P is .1.0.

The percent by weight of the fatty acids, the saponification value andiodine-value of the phosphatides and theneutral equivalent and-iodinevalue of the fatty acids is ameasure and description of the average ofthe fatty .acids present.

Among the most significant figures are those of choline, serine, andethanolarnine, which can be translated into the parent compounds. It isalso evident that for a pure .compound the molecular ratio of one ofthese constituents, e.g., chloine in thecase of lecithin, to P is unity.The value for inositol is also important, as the present state ofknowledge indicates that it is an integral part of several phosphatideswhose structures have not been definitely determined.

In the-soya phosphatide fraction of the present invention, theproportion of lecithin has been increased while the proportion ofcephalin components, especially the inositol, have been reduced. This issuggestive that inositol might be the undesirable active ingredient, butat the present time this is merely a good guess.

In the analysis, the present soya phosphatide fraction .is a materialhaving approximately this composition which does not cause a fall intheblood pressure of the anesthetized cat.

The following examples are illustrative of the composition of thepresent invention but are not to be construed as limiting.

EXAMPLE 1 veloped with 95 percent aqueous ethanol. Fractions were taken.

-m1. gm.

No. 1 595 1. 0 No. 2 1, 016 6. 0 No. a 616 1. 9 No. 1 2, 317 2. 1

Fraction No. 2 was concentrated under reduced pressure for removal ofalcohol. The residue was taken up in suflicient water to give a 1.2percent solution, We of the solution wasused to make up a five percentdextrose preparation, A2 of which was autoclaved. When these .threesolutions were injected into anesthetized cats through a jugular canula,they were found to be free of blood pressure depressor activity. I

EXAMPLE 2 .Ten grams of an alcohol-soluble fraction of soya phosphatideswere dissolved in 100 milliliters of aqueous ethanol 95 percent. Twentygrams of aluminum oxide (Merckchromatographic) was added, and themixture The solution was decanted and filtered. The alcohol was removedunder reduced pressure and the residue taken up in twenty milliliters.

solution of the materialin a five percent aqueous glucose solution didnot depress blood pressure in the eat when injected at a level of 0.5 tofive milliliters per kilogram.

EXAMPLE 3 300' grams of an alcohol-soluble fraction of soya phosphatide(Glidden Lecithin RAS) were dissolved in 1500 milliliters of aqueousethanol percent on a steam bath. The solution was allowed to come toroom temperature. A gummy plastic residue which separated was removed bycentrifugation. 1380 milliliters of solution were recovered. It wasdivided into two parts. 700 milliliters were placed in the refrigeratorfor six days. A heavy liquid layer settled to the bottom. Thesupernatant was decanted and to milliliters of the supernatantcontainring 9.3 grams of solids were added 18.6 grams of aluminum oxide,Merck chromatographic. The mixture was shaken for thirty minutes. Afterremoval of the aluminum oxide and alcohol, a 1.2 percent solution of theresidual material was made in a five percent aqueous solution ofdextrose. Five milliliters per kilogram injected into a cat gave noblood pressure depressor effect. The unrefrigerated portion of theoriginal solution, 680 milliliters, was allowed to stand at roomtemperature one day. Unidentified amorphous material separated and wasfiltered off. The solution, containing 82.6 grams of solids, was stirredthirty minutes with 165.2 grams of aluminum oxide. After removal of thealuminum oxide and alcohol, a 1.2 percent solution of a portion of theresidue was made in a five percent aqueous solution of I glucose. Fivemilliliters per kilogram did not lower blood pressure in cats.

EXAMPLE 4 1235 milliliters of an alcohol solution containing 61.2 gramsof soya phosphatide were stirred with 30.6 grams .of aluminum oxide,Merck. A sample of the solution containing 1.29 grams of phosphatide wasremoved (1). To the remaining solution 29.95 grams more aluminum oxidewere added and stirred-for thirty minutes. A sample was-removed (2).

To themain solution another 23.2 grams of aluminum oxide -were'added andthe process repeated (sample 3). Finally, another 21.5 grams of aluminumoxide were added-to the remaining solution and stirred thirty minutesSix kilograms of alcohol-soluble phosphatide (Glidden Lecithin GradeRAS) were extracted by stirring with r sixty liters of aqueous alcohol(95 percent) for fifteen minutes. This was allowed to settle, and thesupernatant was siphonedotf. Twelve kilograms of aluminum oxide (Harshawcatalytic grade) were added to the supernatanhand the, mixture vstirredfor thirty minutes. The mixture was allowed to settle, and thesupernatant filtered through an alcohol-washed Seitz filter pad. .SixtyV liters of solution containing 2830 grams of the soya phos phatidefraction were obtained. The alcohol from.=55.5

litersof this solution was removed in a flash, still, 72

pounds of cottonseed. oil being added during the process,

7 Using this oil-phosphatide solution, the following quantities ofmaterials were prepared into an emulsion:

1.2% soya phosphatide fraction grams 2400 15% cottonseed oil (WessonOil) pounds 66 4% anhydrous dextrose grams 8000 0.3% Pluronic F 68 do600 Water for injection U.S.P. sutficient to make 200 liters.

Forty liters of water were filtered into a large tank, and thetemperature was raised to ninety degrees centigrade. The dextrose wasadded and followed by Pluronic F 68. This mixture was pumped intoanother large tank. The first tank was washed with filtered water, andthe wash water was also pumped into the second tank. The solution in thesecond tank was filtered back into the first tank. The filter was alsowashed into the first tank, adjusting to approximately eighty liters. Atseventy degrees centigrate the phosphatide-oil solution was added, andvolume was brought up to 120 liters by adding filtered water. Theresulting mixture Was mixed thoroughly for five minutes by rapidstirring and then homogenized at 4000 pounds per square inch for twentyminutes at seventy degrees centigrade, recycling into the first tank.Meanwhile, eighty liters of water were placed in the second tank. Thewater from the second tank was added to the emulsion at seventy degreescentigrade. With pressure at 4000 pounds per square inch, the mixturewas homogenized with a Manton-Gaulin homogenizer into tank 2. The lastcycle was repeated twice, and the resulting emulsion was filtered into600 milliliter centrifuge bottles. The emulsion was autoclaved atfifteen pounds per square inch for twenty minutes and cooled as rapidlyas possible.

This emulsion did not cause a fall of blood pressure in anesthetizedcats and was free of serious clinical reactions when injectedintravenously into human beings.

emulsion made with the same phosphatide prior to treat- EXAMPLE 7 Inorder to characterize the soya phosphatide fraction of the presentinvention and to compare it with other fractions as well as with thewhole soya phosphatides, the process of the present invention was usedto prepare material for chemical analyses.

1040 grams of an alcohol-soluble fraction of soya phosphatide (GliddenLecithin RAS) were dissolved in ten liters of aqueous-ethanol (95percent) and stirred twenty minutes. The solution was allowed to settle.A gummy, plastic residue which separated was discarded after decantationof the supernatant. 10,700 milliliters of supernatant were recovered.The alcohol was removed from part of this supernatant and the residueanalyzed. The results of the analyses appear under the column headedRAS/Al in Table I. To 300 milliliters of the supernatant were addedsixty grams of aluminum oxide, Merck chromatographic, and the mixturewas shaken for thirty minutes. After removal of the aluminum oxide andalcohol, the residue was analyzed and possessed the analytical valuesshown in Table I. To still another BOO-milliliter portion of thesupernatant was added grams of activated carbon (Norit-SG) and themixture was shaken for thirty minutes. The carbon was filtered oif; andsince the filtrate still possessed a trace of color, it was again shakenfor thirty minutes with an additional fifteen grams of activated carbon.The carbon was removed by filtration leaving a colorless filtrate andthe alcohol was removed in vacuo yielding 2.48 grams of material. Thismaterial was analyzed and possessed the analytical values shown in TableI.

Table I ANALYSES 0N VARIOUS PHOSPHATIDES Glidden Glidden A1 0; ActivatedEgg 1 lilianahiin Lecithin, Lecithin, RAS/Al 7 Treated Carbon 4 Phos. Eg

RC 5 HAS 6 Treated Lecit Tot. Nitrogen, percent 1. 15 1.23 1.38 1.441.45 4.15 1.79 Tot. Phosphorus, percent- 3. 45 2.44 2. 48 3.01 2.84 6.313.90 Choline, percent 3. 00 6. 23 7. 16 10. 10.04 13.85 15.30 Inositol,percent 2. 41 0.207 0.08 0.01 0.04 .02 Ethanolamine, percent"- 1.9 1. 30. 93 0.47 0.4 0.30 0 Serine. percent 0.41 0.10 0. 11 0. 045 0.4 0. 20 0Iodine value (of whole tra 76. 1 92. 2 82.0 85.9 69.4 11.2 88.0 Ash,percent (P20 8. 57 3. 42 3. 28 2. 61 3. 00 16. 72 N;P moi. ratio 0.736 1. 112 1. 23 1.026 1. 128 i 1.440 1.00 Reducing Sub.'- (ofhydrolyzed material). 13. 7 6. 7 2. 16 28.3 Fatty acids, percent 55. 867. 1 66. 1 70. 7 47. 8 19 3 70.0 Iodine Value (of fatty acid) 124. 7115. 5 116. 7 118. 2 105. 8 91.0

1 Treated with A1 0; and activated carbon. This material still possessedthe blood pressure depressor action in an anesthetized Folin-Wu assayused. J. Biol. Chem. 41, 367 (1920).

5 A commercial solid soya phosphatide mixture containing essentially allof the phosphatides as they occur in the soybean and difiering from thefluid preparations (the lecithins" of commerce) in a lower oilcontent-approximately four percent.

1 A commercial source of the alcohol-soluble fraction of the mixed soyaphosphatides, having a higher content of lecithin and less of thecephalin fraction than RG.

7 Upon extracting HAS with 10 v./w. of alcohol 95 percent, we find thatonly about seventy percent of the material is now soluble. This 13reflected in the reduced quantities of phosphatidylinositol andethanolamine found which are the main components of the cephalinfraction.

EXAMPLE 6 The following quantities of materials were made into anemulsion in a Cherry-Burrell homogenizer.

Prepared in the manner described in Example 5.

Repeated injections of this emulsion into cats at five to tenmilliliters/kilogram has shown no evidence of de- The procedures usedfor determining the various values shown in Table I were as follows:Total nitrogen, Micro- Kjeldahl; Phosphorus, Fiske and SubbaRow, J.Biol. Chem., 66,375 (1925); Choline, D. Glick, J. Biol. Chem., 156, 643(1944); Ethanolamine and Serine, separated by procedure of C. Artom, J.Biol. Chem., 157, 585 (1945), with determination by an adaptation of S.Moore and W. H. Stein, J. Biol. Chem. 211, 907 (1954); Inositol,adaptation of the pyridoxine method of Atkin et al., (Anal. Ed) Ind.Eng. Chem., 15, 141 (1943), using Sacch. carlsbergensis, ATCC 9080;Fatty Acids, two hour hydrolysis with 2 N sodium hydroxide in fiftypercent ethanol followed by acidification and extraction with pepressoractivity, whereas 0.1 milliliter/kilogram of 3.11 troleum ether; andiodine value, U.S.P.

It may be concluded from the table that the purified fraction of soyaphosphatides obtained by the present process is a mixture ofphosphatidylcholine (lecithin), phosphatidylethanolamine, andphosphatidylserine. Lecithin is the predominant constitutent.Phosphatidylinositol is essentially absent which may well be asignificant characterizing feature. Circumstantial evidence indicatesthat phosphatidylinositol is the reactive or most reactive agent whichproduces a fall in the blood pressure of the anesthetized cat, 1)because there is a rough parallelism between the amount present in thevarious materials tested and their resp-ctive activities, and (2) afifty percent concentrate of phosphatidylinositol was found to be highlyactive.

It is to be understood that the invention is not to be limited to theexact details of operation or compositions shown and described, asobvious modifications and equivalents will be apparent to one skilled inthe art, and the invention is therefore to be limited only by the scopeof the appended claims.

We claim:

1. A therapeutic fat product which is especially suitable forintravenous use in human beings, which product comprises ametabolizable, non-toxic, fixed oil emulsified in an aqueous vehicle bya soya phosphatide fraction which (1) is stable; (2) iswater-dispersible; (3) is vegetable oil-soluble; (4) is monatomiclower-molecular weight aliphatic alcohol-soluble; and (5) is prepared byadsorbing undesirable reactive materials found in monatomic lowermolecular weight aliphatic alcohol-dissolved soya phosphatides on anadsorbent selected from the group consisting of aluminum oxide,magnesium oxide and activated carbon. 7

2. The composition of claim 1 which contains in addition anintravenously compatible sugar as an isotonic agent and an intravenouslycompatible ethylene oxidepolypropylene glycol condensation product as aco-emulsi fier.

3. A therapeutic fat product which is especially suitable forintravenous use in human beings, which product comprises ametabolizable, non-toxic,'fixed oil emulsified in an aqueous vehicle bya stable, water-dispersible, vegetable oil-soluble soya phosphatidefraction (1) which is prepared by adsorbing undesirable reactivematerials found in ethanol-dissolved soya phosphatides on aluminum oxideand (2) which has the following approximate composition:

4. The composition of claim 3 which contains in addition anintravenously compatible monosaccharide as an isotonic agent and anintravenously, compatible ethylene oxidepolypropylene glycolcondensation product as a coemulsifier.

5. A therapeutic fat product which is especially suitable forintravenous use in human beings, which product comprises ametabolizable, non-toxic, fixed oil, emulsified in an aqueous vehicle bya stable, water-dispersible, vegetable oil-soluble soya phosphatidefraction 1) which is prepared by adsorbing undesirable reactivematerials found in ethanol-dissolved soya phosphatides on non-acidsactivated carbon and (2) which has the following approximatecomposition:

Total nitrogen percent 1.45 Total phosphorus do 2.84 Choline do 10.04Inositol do 0.04 Ethanolamine dO 0.4 Serine do 0.4 Iodine value (oftotal composition) 69.4 N P Molecular ratio 1.128 Reducing substance (asbalactose) percent 28.3 Fatty acids do 47.8 Iodine value (of fattyacids) 105.8

6. The composition of claim 5 which contains in addition anintravenously compatible monosaccharide as an isotonic agent and anintravenously compatible ethylene oxide-polypropylene glycolcondensation product as a co-emulsifier.

7. A therapeutic fat product which is especially suitable forintravenous use in human beings, which product comprises about fifteenpercent weight/volume of cottonseed oil emulsified in an aqueous vehicleby about 1.2 percent Weight/volume of a stable, water-dispersible,vegetable oil-soluble soya phosphatide fraction which is prepared byadsorbing undesirable reactive materials found in ethanol-dissolved soyaphosphatides on aluminum oxide, about four percent weight/volume ofdextrose, and about 0.3 percent weight/volume of an ethyleneoxide-polypropylene glycol condensation product of the formula HO(C H O)(C H O) (C H O)H with a polypropylene-base molecular weight of about1750 and a total molecular weight of about 8750.

References Cited in the file of this patent UNITED STATES PATENTS OTHERREFERENCES Meng et al.: J. Lab. and Clin. Med. 33:6, pp. 689-707, June1948.

Waddell et al.: J. Lab. and Clin. Med. 45:5, pp. 697- 710, May 1955.

Chem. and Eng. News, 28:10, p. 3428, October 2, 1950.

Gorens: J. Lab. and Clin. Med., vol. 34, pp. 1627- 1633 (1949).

Holman: Progress in the Chem. of Fats and Other Lipids, vol. 3, 1955,Pergamon Press, N.Y., pp. 2-17.

1. A THERAPEUTIC FAT PRODUCT WHICH IS ESPECIALLY SUITABLE FORINTRAVENOUS USE IN HUMAN BEINGS, WHICH PRODUCT COMPRISES AMETABOLIZABLE, NON-TOXIC, FIXED OIL EMULSIFIED IN AN AQUEOUS VEHICLE BYA SOYA PHOSPHATIDE FRACTION WHICH (1) IS STABLE, (2) ISWATER-DISPERSIBLE, (3) IS VEGETABLE OIL-SOLUBLE, (4) IS MONATOMICLOWER-MOLECULAR WEIGHT ALIPHATIC ALCOHOL-SOLUBLE, AND (5) IS PREPARED BYADSORBING UNDERSIRABLE REACTIVE MATERIALS FOUND IN MONATOMIC LOWERMOLECULAR WEIGHT ALIPHATIC ALCOHOL-DISSOLVED SOYA PHOSPHATIDES ON ANADSORBENT SELECTED FROM THE GROUP CONSISTING OF ALUMINUM OXIDE,MAGNESIUM OXIDE AND ACTIVATED CARBON.